Analytes in a body fluid sample, in particular blood, which is obtained by a wound in the skin of a patient, are determined in many fields of medical analysis. In the case of drawing the body fluid from a body part, preferably from the fingertip, small quantities of the body fluid are sufficient to determine an analyte, for example, the glucose content, for medical and diagnostic purposes. The employed instruments are constructed so that they are readily usable not only by medical technicians, but rather also by laypersons.
Two steps are necessary to determine an analyte in a body fluid sample flowing out of a body part. Firstly a wound must be produced by a prick in the skin of a body part, which can be performed by means of a lancing instrument, for example. In a second step, the body fluid is received and analyzed in an analysis instrument. The use of two instruments operating independently of one another is uncomfortable and cumbersome for the user. Therefore, combined systems have been developed, which unify the two instruments known in the art into one instrument and may execute both steps. The known instruments are relatively large, however.
New developments comprise integrated analysis systems. The typically automated instruments allow a “one-step treatment”, so that the user must only apply the system once and can read off the analysis results—without further handling steps.
In a first type of such integrated systems, separate puncturing elements and analysis elements are used. Within a combined piercing and analysis instrument, the required movements for piercing into the skin and for transferring a sample liquid droplet thus acquired onto the analysis system are implemented by means of a movement mechanism integrated in the instrument. The blood transfer from the produced wound to the analysis element is difficult to implement. It is to be considered that modern instruments are to work by means of extremely small blood quantities. Further problems relate to the movement and coupling mechanism of the lancets and puncturing elements.
The problems with the transport of very small blood quantities are reduced and the mechanism of the instrument is simplified if, instead of separate puncturing elements and analysis elements, integrated sample acquisition and analysis elements are used, in which the puncturing element and the analysis element are unified in a disposable unit. Because of these features, systems having such integrated sample acquisition and analysis elements have predominantly been proposed in recent time.
Examples are described in the following publications:    1) WO 2006/092281 A1    2) US 2003/0212345 A1    3) U.S. Pat. No. 6,607,658 B1
The present disclosure is directed to improved systems which are compact in overall size and cost-effectively produced. As such, the disclosed analysis system has the features as claimed.
The analysis system according to the disclosure for determining an analyte in a body fluid sample acquired through a prick in the skin comprises a magazine having chambers and a reusable analysis instrument having a puncturing drive, a mounting for receiving the magazine, and a measuring and evaluation unit.
In its chambers, the magazine contains analysis elements having a sample contact zone and a reagent system containing at least one reagent, whose reaction with the body fluid results in a measurable change of a measuring variable, and puncturing elements having a tip for piercing into the skin having a capillary channel, which forms a fluid connection between the tip and a sample transfer zone of the puncturing element.
The puncturing drive of the analysis system drives a puncture movement of a puncturing element on a movement path, which comprises a propulsion phase in the puncturing direction and, after reaching a reversal point of the puncture movement, a retraction phase opposite to the puncturing direction. The magazine can be received in the mounting of the analysis instrument in such a manner that one chamber of the magazine at a time is located in a functional position, in which a puncture movement in the chamber can be moved by the puncturing drive. The measuring and evaluation unit is set up to measure the measurable change of a measuring variable and to ascertain the desired analysis result.
According to the present disclosure, the magazine comprises two partial magazines, namely a puncturing element partial magazine having puncturing element chambers, which each contain one puncturing element, and an analysis element partial magazine having analysis element chambers, which each contain one analysis element. The puncturing elements and the analysis elements are thus contained in separate chambers—at least in the delivery state of the magazine, preferably always.
The puncturing element chamber has a puncturing element exit opening. The analysis element chamber has a puncturing element entry opening, which is sealed by means of a sealing film. When the magazine is located in the functional position, the two partial magazines are positioned relative to one another or may be brought into a position such that one puncturing element exit opening is adjacent to one puncturing element chamber and one puncturing element entry opening is neighboring to one analysis element chamber such that the two openings align and a puncturing element can be moved from the puncturing element chamber through the puncturing element exit opening and the puncturing element entry opening into the adjacent analysis chamber. The sealing film, which seals the puncturing element entry opening of the analysis element chamber at least in the delivery state, is opened, for example, punctured, before or during the puncture movement of the puncturing element from the puncturing element chamber into the analysis element chamber. Punctured is used as opened hereafter without restriction of the generality.
The piercing and puncturing of the sealing film can preferably be performed by the puncturing element itself. However, the film can also be opened by another element before the puncturing element exits from the puncturing element exit opening.
The two-part magazine having puncturing element partial magazine and analysis element partial magazine permits the differing and sometimes contrary requirements of the analysis elements and puncturing elements to be taken into consideration. The puncturing element can be sterilized separately, for example, using beta radiation, without the analysis elements also being subjected to the radiation. For example, the puncturing element partial magazine can be equipped with puncturing elements before the assembly with the analysis element partial magazine. The puncturing element exit opening is preferably sealed by means of a sterile cling film, so that the puncturing element chambers are sealed. The sealing is preferably executed before the sterilization of the puncturing element partial magazine and after the puncturing element chambers are equipped with a puncturing element. The puncturing element partial magazine is subsequently subjected to the beta radiation, so that all puncturing elements are sterilized. Because the analysis elements having the included reagents are contained in a separate partial magazine, they are not damaged by the radiation during the sterilization of the puncturing element partial magazine.
According to the present disclosure, the movement path of the puncturing element includes a transfer position within the chamber, in which the sample transfer zone of the puncturing element is adjacent to the sample contact zone of the analysis element, in order to produce a fluid connection to transfer a body fluid sample from the puncturing element to the analysis element. A fluid contact between the puncturing element and the analysis element therefore exclusively occurs in the transfer position of the puncturing element, in which it is located in the analysis element chamber. In other positions of the puncturing element on its movement path, no fluid transport to the analysis element can take place. In this manner, an exactly controlled fluid transfer can occur. In addition to the location-dependent control a time-dependent control is also possible. For example, the puncturing element can remain for a specified time in the transfer position, for example, to make possible a fluid transport into the sample transfer zone of the puncturing element, before the puncturing element and the analysis element are neighboring to one another in such a manner that the sample transfer takes place. A force-controlled blood transfer is also possible in a preferred embodiment.
The puncturing element and the analysis element are preferably moved toward one another for this purpose until they preferably contact one another. The relative movement between the two elements can be performed by a transverse movement (in relation to the puncturing direction) of one of the two elements, preferably by a transverse movement of the puncturing element.
In another embodiment, the relative movement between the analysis element and the puncturing element is caused by a pivot movement of the connection element, which is coupled to the puncturing element and produces a connection between the puncturing element and the puncturing drive. The connection element at least partially extends into the puncturing element chamber. The pivot movement of the connection element can be implemented by a control curve of the drive mechanism, for example. A movement of the connection element transversely to the lancing apparatus is also conceivable.
A plurality of steps are executed according to the present disclosure during the production of the two-part magazine, whose sequence can deviate from the sequence specified here or in which the individual steps may be combined and/or executed jointly.
At the beginning of the production process, the two partial magazines are separate from one another. The puncturing element partial magazine is equipped with puncturing elements. Both the puncturing element exit opening and also the connection element entry opening of each puncturing element chamber are sealed by means of a sealing film each. The puncturing elements contained in the puncturing element partial magazine are sterilized in a further step. In another step, the two partial magazines are connected or coupled to one another. The partial magazines may be connected so they are movable relative to one another. The partial magazines are preferably connected to one another in such a manner that a relative rotational movement between them is prevented. The sealing film of the puncturing element exit opening can also seal the puncturing element entry opening of the analysis element partial magazine.
A further method step comprises the sealing of the analysis element chambers of the analysis element partial magazine on its puncturing element entry opening and on its magazine outlet opening by means of a sealing film each. Another production step provides equipping the analysis element partial magazine with analysis elements. The equipping is performed before the complete sealing of the analysis element chambers or before the sealing of one of the openings. The analysis elements are preferably positioned in a mounting in the chambers.
The individual production steps may vary in their sequence, in particular, both partial magazines may be equipped before their connection. During the production, the puncturing element partial magazine should be sterilized when the analysis element partial magazine is still separate.
In one embodiment of the method, the sealing of the puncturing element entry opening of each analysis element chamber by means of a sealing film occurs before the two partial magazines are connected to one another. Both partial magazines are preferably equipped and sealed separately from one another and only subsequently assembled.
In one embodiment of the method, the rotational fixation of the two partial magazines is first produced during use of the magazine in the analysis system or the reusable analysis instrument.
In the case of one-part magazines, which have a common chamber for puncturing element and analysis element, the problem that the radiation used for sterilization can damage the reagents of the analysis elements and make them partially unusable is solved in that the reagent quantity is increased in the analysis element. A sufficient quantity of functional reagents then remains in the analysis element upon the sterilization, so that a determination of an analyte in the fluid sample can be performed. However, the use of an increased reagent quantity results in significant additional costs.
A further feature of separate partial magazines is that no reagent of the reagent system of the analysis elements comes into contact with the puncturing elements, in particular not during the production or storage. Because the reagents are not allowed to enter the skin, it is important that the puncturing elements are not contaminated.
In addition to the possibility of separate production and sterilization, the analysis system according to the disclosure also permits the two partial magazines to be optimized for the respective requirements. The material for the analysis element partial magazine should form a very good water vapor barrier, so that the analysis elements are kept dry. During the use of photometric analysis elements, the material of the partial magazine should be at least partially, preferably completely transparent. The analysis element partial magazine is preferably produced from a transparent, see-through plastic, in any case the transparent area. Polymer materials are suitable, preferably a cycloolefin copolymer, i.e., an amorphous, transparent copolymer based on cyclic and linear olefins, which are also distinguished by a high transparency, good moisture barrier, and high rigidity with little warpage.
The material of the puncturing element partial magazine should not contain additives which impair the puncturing element and its layer, which is typically hydrophilic. The material also should not be damaged by the (beta) radiation used for sterilization of the puncturing elements.
Both partial magazines preferably comprise plastic materials and are preferably produced in the injection molding method. The plastics are selected in accordance with the requirements.
In the context of the disclosure, it has been established that the use of integrated sample acquisition and analysis elements as described in cited documents (1) to (3) has significant disadvantages. The integration results in increased production costs. In addition, there exists the risk of contamination of the lancing tip of the sample acquisition part by reagents of the analysis part. A two-part magazine according to the present disclosure provides separate lancing and analysis elements, but simultaneously allows a compact construction and simple mechanical design.
The magazine according to the disclosure is preferably a drum magazine, which has a puncturing element partial drum and an analysis element partial drum. The use of a magazine drum allows a very compact construction in particular. Magazine drums appear to be the most promising and attractive concept according to the current state of knowledge with respect to the system size, in relation to the number of possible tests for determining the analyte. Alternatively, the magazine can be a (cuboid) linear magazine.
In one embodiment of the magazine having two partial magazines, three barrier films are provided, namely a first, through which a connection element can be coupled onto the puncturing element, a second, which is positioned between the two partial magazines and separates the puncturing element chamber from the analysis element chamber, and a third, through which the puncturing element can exit from the magazine on its (linear) movement path in the puncturing direction. The magazine preferably has four barrier films, so that each front face of the partial magazines is sealed by means of a film.
The present disclosure is explained in greater detail hereafter on the basis of embodiments shown in the figures. The features shown therein may be used individually or in combination to provide embodiments of the disclosure. The described embodiments do not represent a restriction of the generality of the subject matter defined in the claims.